SLC36A1

Chr 5

solute carrier family 36 member 1

Also known as: Dct1, LYAAT1, PAT1, TRAMD3

NCBI Gene: 206358 ENSG00000123643 UniProt: Q7Z2H8 OMIM: 606561

The protein functions as an electrogenic proton/amino acid symporter with selectivity for small neutral amino acids and GABA, and may be involved in lysosomal amino acid efflux and neuronal exocytosis. Mutations cause autosomal recessive iminoglycinuria with hyperglycinuria, a benign renal transport disorder typically presenting in childhood with elevated glycine and imino acids in urine. The gene shows low constraint to loss-of-function variation, consistent with the mild clinical phenotype.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.90

Clinical Summary— SLC36A1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.000

Z-score 1.92

OE 0.57 (0.37–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.38Z-score

OE missense 0.77 (0.69–0.86)

220 obs / 285.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.37–0.90)

0≤0.351.4

Missense OE?0.77 (0.69–0.86)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 13 / 22.9Missense obs/exp: 220 / 285.6Syn Z: 0.03

This gene — mechanism propensity

0.77top 25%

GOF

0.82top 10%

LOF

0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.